Pre-hospital proton pump inhibitor use and clinical outcomes in hospitalized COVID-19 patients: A retrospective case-control study

BACKGROUND Proton pump inhibitors (PPIs) are among the most commonly prescribed medications globally. While concerns exist regarding their association with adverse infection-related outcomes, their impact on coronavirus disease 2019 (COVID-19) severity remains uncertain. Emerging preclinical data suggest immunomodulatory and antiviral properties of PPIs, yet clinical evidence is conflicting. AIM To investigate whether chronic pre-hospital PPI use is associated with improved outcomes in patients hospitalized with COVID-19. METHODS We conducted a retrospective case-control study of adult inpatients with severe acute respiratory syndrome coronavirus 2 infection admitted to a racially and ethnically diverse community hospital in Massachusetts from July 2021 to March 2022. Patients were stratified by documented pre-hospital PPI use. The primary outcomes were intensive care unit (ICU) admission, need for invasive mechanical ventilation, and in-hospital mortality. Multivariable logistic regression was used to adjust for demographics, comorbidities, and treatment variables. Significance was set at P < 0.05. RESULTS Among 248 patients, 83 (33.4%) were on PPIs prior to hospitalization. Compared to non-users, PPI users had significantly lower rates of ICU admission (13.3% vs 24.8%, P = 0.034), mechanical ventilation (13.3% vs 25.5%, P = 0.027), and in-hospital mortality (6.0% vs 17.6%, P = 0.013). Multivariable analysis confirmed these associations: ICU admission [adjusted odds ratios (aOR): 0.462, 95%CI: 0.223–0.955], mechanical ventilation (aOR: 0.447, 95%CI: 0.216–0.923), and mortality (aOR: 0.144, 95%CI: 0.031–0.677). Findings were consistent across demographic and comorbidity strata. CONCLUSION In this diverse, real-world United States cohort, chronic pre-hospital PPI use was independently associated with lower odds of intensive care unit admission, mechanical ventilation, and mortality among COVID-19 inpatients. These findings highlight a potentially protective role of PPIs and support continued therapy in eligible patients.